In response to Challenge Area 04: Clinical Research and specific Challenge Topic 04-DC-101: Prevention of Otitis Media, we propose a clinical trial of a preparation of viscous xylitol with a mucosal adherence agent for the prevention of acute otitis media (AOM) in otitis-prone children. AOM is one of the most common illnesses of childhood, with a peak incidence between six and 24 months of age;it is also the most common indication for antibiotic use among U.S. children, and as such, contributes significantly to the growing problem of antimicrobial resistance. A safe and effective means of preventing AOM without the use of antibiotics would be of great public health importance. Xylitol, a naturally-occurring sugar alcohol, has been proposed as a preventative therapy for AOM. In two well-designed, randomized, placebo-controlled clinical trials conducted by a single research team in Finland, daily treatment with xylitol five times daily for two to three months was found to reduce the incidence of AOM in children by 30-40%, and to reduce antibiotic use by 21-36%. Older children consumed xylitol in the form of a chewing gum or lozenge, while children too young to chew gum received xylitol as simple aqueous solution. A further trial conducted by the same Finnish research team of their xylitol aqueous solution given three times daily did not show any effect of AOM. Based on scientific evidence that less frequent xylitol administration may be effective in preventing AOM if higher doses are use, on pilot clinical research that we have done demonstrating that such higher doses can safely be used in young children, and on the basis of a new commercially-available form of viscous xylitol syrup with the addition of a mucosal adherence agent ("xylitol syrup"), we propose to conduct a pragmatic practice-based randomized placebo-controlled trial of xylitol syrup given three times daily for 12 weeks to children 6 months to 5 years of age with a history of recurrent AOM. The study will be fielded in 28 primary-care pediatric practices selected from The Pediatric Physicians'Organization at Children's and the Slone Center Office-based Research Network. The primary outcome of the study will be a comparison of the incidence of clinically-diagnosed episodes of AOM in xylitol-treated subjects versus placebo-treated controls;secondary outcomes will include a comparison of overall antibiotic use between the study groups, and a comparison of nasopharyngeal and oropharyngeal colonization with bacteria that cause AOM in a subset of 200 subjects. The proposed study is an attempt to use a novel preparation of xylitol syrup to prevent ear infections in children with recurrent ear infections. We plan to perform a clinical trial in which we will give children with a history of recurrent ear infections either the novel preparation of xylitol syrup or a matching placebo three times a day for 12 weeks to determine if this treatment reduces the chance of getting further ear infections.